Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
Name
elife-56782-v2.pdf
Description
Published version
Size
4.68 MB
Format
Adobe PDF
Checksum (MD5)
ec7b087cd3dd0b3ef0322e9b5b29ddbe
Author(s)
Lau, Allison N
Li, Zhaoqi
Danai, Laura V
Westermark, Anna M
Darnell, Alicia M
Ferreira, Raphael
Gocheva, Vasilena
Sivanand, Sharanya
Lien, Evan C
Sapp, Kiera M
Date Issued
2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
© Lau et al. Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid- fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.56782
